This is an ongoing clinical trial whose primary objectives are to determine if sodium fluoride (NaF) and calcium (Ca) therapy for postmenopausal osteoporosis is safe and is efficacious in reducing the incidence of vertebral fractures. Secondary objectives are to assess the effect of therapy on bone mineral density (BMD) of the spine and hip; to determine if skeletal response of individual patients (pts) to treatment varies and, if so, what factors relate to therapeutic outcome; to study the incidence and causes of impaired bone mineralization during fluoride therapy; and to assess the effect in the occurrence of non-vertebral skeletal fractures. 202 osteoporotic women, ages 50 to 75 years, were randomly assigned to parallel treatment and control arms. Pts in the treatment arm receive 75 mg daily of NaF in divided doses whereas the control pts take a matching placebo. Pts in both treatment and control arms receive 1.5 g daily of Ca as CaCO3 in divided doses. Treatment is continued for 4 years (yrs). Safety is assessed by continued contact with the pts, by interview and examination every 6 months, and by evaluation with standard laboratory tests every yr. The number and degree of new vertebral fractures in the two arms are assessed by the new and precise method of quantitative biplanar roentgenography. Individual resposiveness to therapy will be assessed by serial determinations of BMD of lumbar spine, midradius and proximal femur by single and dual photon absorptiometry and by measurement of biochemical bone markers including serum bone Glaprotein. Selected groups will have metabolic balance studies for F-bioavailability and iliac crest biopsies for quantitative bone histology and for F-content. We will need a continuation of 3-yrs to complete the pt studies; complete the laboratory measurements; check and verify the 400,000 data elements that will have been collected; and complete data analysis. While this is being accomplished we will extend the treatment arm pts; for an additional 2 yrs to provide data that are needed to answer certain crucial questions on long-term skeletal effects of F-treatment. During the continuation period, we also will perform measurements (serum 1,25(OH)2D, osteonectin and other new biochemical bone markers, urine cyclic AMP and 6-yr bone biopsies) on urine and serum samples stored at -70 degrees C. These measurements are in addition to those proposed in the original application.